Highly dangerous Cryptococcus fungi love sugar and will consume
it anywhere because it helps them reproduce. In particular, they thrive
on a sugar called inositol which is abundant in the human brain and
spinal cord.

To borrow inositol from a person's brain, the fungi have an expanded
set of genes that encode for sugar transporter molecules. While a
typical fungus has just two such genes, Cryptococcus have
almost a dozen, according to Joseph Heitman, M.D., Ph.D., chairman of
the Duke Department of Molecular Genetics and Microbiology.

"Inositol is abundant in the human brain and in the fluid that bathes
it (cerebral spinal fluid), which may be why this fungus has a
predilection to infect the brain and cause meningitis," Heitman said.
"It has the machinery to efficiently move sugar molecules inside of its
cells and thrive."

The findings on Cryptococcus genes were published online
this week in the inaugural issue of mBio, a new open access microbiology
journal.

This specialized brain attack likely occurred because these fungi
adapted to grow on plants in the wild, which also are abundant in
inositol, said lead author Chaoyang Xue, Ph.D., formerly a postdoctoral
research associate in the Heitman lab and now an assistant professor at
the Public Health Research Institute at the University of Medicine and
Dentistry of New Jersey (UMDNJ). "In fact, this pathogenic yeast has
more inositol transporters than all other fungi we have compared it to
in the fungal kingdom, based on what we know from genome research."

The team of researchers discovered that inositol stimulates Cryptococcus
to sexually reproduce. "A connection between the high concentration of
free inositol and fungal infection in the human brain is suggested by
our studies," Xue said. "Establishing such a connection could open up a
new way to control this deadly fungus."

Cryptococcus' love for sugar may also be a fungal Achilles
Heel, Heitman said. "Now scientists may be able to target the fungi by
developing ways to put them on the fungal equivalent of an Atkin's
low-carbohydrate diet so they will stop multiplying." He said
researchers could use the new findings to devise different types of
strategies to block Cryptococcus infections.

These studies will be reported in the inaugural issue mBio,
which will be launched in May by the American Society of Microbiology as
an online journal that spans all areas of microbiology.

Other authors include Lydia Chen and Wenjun Li of the Duke Department
of Molecular Genetics and Microbiology; Tongbao Liu of the Public
Health Research Institute, University of Medicine and Dentistry of New
Jersey; Iris Liu and James Kronstrad of Michael Smith Laboratories,
University of British Columbia; and Andreas Seyfang of the Department of
Molecular Medicine at the University of South Florida.

This work was supported by National Institute of Health/National
Institute of Allergy and Infectious Disease grants. This work was also
supported by the new Investigator institutional start-up fund from
UMDNJ.